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Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection

Figure 6

Cellular immune responses drive early low-frequency quasispecies diversity.

(A) For each protein, the average frequency of non-dominant baseline residues of positions within the 19 described CD8 epitopes restricted by subject 9213's HLA alleles (left) and outside of the 19 described epitopes (right) is plotted for each time point sequenced. Colored lines denote the proteins for which diversity was substantially higher inside of CD8 epitopes versus outside CD8 epitopes. (B) To determine rates of viral escape for each epitope escape mutations were defined as any amino acid substitution within the epitope. Symbols denote the cumulative observed frequency of all escape mutations, and lines depict the best fit by non-linear regression of the observed frequency data to the CTL escape model of Asquith et al. [65]. Open symbols and dashed lines denote epitopes for which evolution was consistent with reversion. Black symbols and dotted lines denote epitopes for which there was no evidence of escape. CD8 responses against each epitope are shown in parentheses in the legend and were measured by IFN-gamma Elispot assay (Spot Forming Cells/Mill PBMC (SFC)). (C) Frequency of wild-type (black) and variant (red) haplotypes of the Vif B38-WI9 epitope and flanking regions over time. Shown at the top is the clade B consensus sequence for reference. (D) Frequency of wild-type (black) and variant (red) haplotypes of the Nef A24-RW8 B38-WI9 epitope and flanking regions over time. Blue residues highlight differences between the day 0 transmitted sequence and HIV-1B consensus sequence.

Figure 6

doi: https://doi.org/10.1371/journal.ppat.1002529.g006